Long-term objectives include a comprehensive understanding of the many components regulating intracranial pressure and their interaction. An important goal, one which we have been working toward during the past several years, is a better understanding of the role of the cerebrospinal fluid (CSF) bulk flow system in the regulation of intracranial pressure. A further goal is that of gaining insight into how exposure to environmental toxins during critical periods in development perturb systems for regulating intracranial fluid dynamics and pressure. Exposure to lead can result in a profound increase in intracranial pressure, particularly in the developing organism. A specific aim of this research proposal is to define the effects of lead on a major mechanism for buffering intracranial pressure, absorption of CSF into the venous circulation. We will use both in vivo and in vitro techniques, and we stress the development aspect of the work from the standpoint of a major health problem, hydrocephalus. Additionally, we propose to explore the link between exposure to lead in utero and the risk for developing abnormal intracranial fluid dynamics. We foresee that information gained from these experiments will be important, but not only in terms of other conditions associated with abnormal intracranial fluid regulation (pseudotumor cerebri, Reye's syndrome, normal pressure hydrocephalus with dementia). There are important implications from the standpoint of therapy for those conditions, if factors which influence CSF absorption, both favorably and adversely, can be defined.